Genetic Variant ADPGK:p.Ala63Thr (chr15-72783505-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001365225.1(ADPGK):c.187G>A(p.Ala63Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,465,286 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A63S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000076 ( 0 hom. )

Consequence

ADPGK
NM_001365225.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.11

Publications

0 publications found

Variant links:

Genes affected

ADPGK (HGNC:25250): (ADP dependent glucokinase) ADPGK (EC 2.7.1.147) catalyzes the ADP-dependent phosphorylation of glucose to glucose-6-phosphate and may play a role in glycolysis, possibly during ischemic conditions (Ronimus and Morgan, 2004 [PubMed 14975750]).[supplied by OMIM, Mar 2008]

ADPGK links:

ADPGK-AS1 (HGNC:44144): (ADPGK antisense RNA 1)

ADPGK-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0057326257).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365225.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADPGK	NM_001365225.1	MANE Select	c.187G>A	p.Ala63Thr	missense	Exon 1 of 7	NP_001352154.1	Q9BRR6-1
ADPGK	NM_031284.5		c.187G>A	p.Ala63Thr	missense	Exon 1 of 7	NP_112574.3
ADPGK	NM_001365227.1		c.187G>A	p.Ala63Thr	missense	Exon 1 of 4	NP_001352156.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADPGK	ENST00000456471.3	TSL:1 MANE Select	c.187G>A	p.Ala63Thr	missense	Exon 1 of 7	ENSP00000397694.3	Q9BRR6-1
ADPGK	ENST00000567941.5	TSL:1	n.187G>A		non_coding_transcript_exon	Exon 1 of 7	ENSP00000458102.1	Q9BRR6-6
ADPGK	ENST00000957653.1		c.187G>A	p.Ala63Thr	missense	Exon 1 of 7	ENSP00000627712.1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000546

AC:

AN:

73266

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.000828

Gnomad AMR exome

AF:

0.000214

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000762

AC:

AN:

1312944

Hom.:

Cov.:

AF XY:

0.00000310

AC XY:

AN XY:

644988

show subpopulations

African (AFR)

AF:

0.000227

AC:

AN:

26412

American (AMR)

AF:

0.000159

AC:

AN:

25232

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21948

East Asian (EAS)

AF:

0.00

AC:

AN:

29778

South Asian (SAS)

AF:

0.00

AC:

AN:

70954

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32484

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3852

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1047824

Other (OTH)

AF:

0.00

AC:

AN:

54460

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000459

AC:

AN:

152342

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.000168

AC:

AN:

41600

American (AMR)

AF:

0.00

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000756

ExAC

AF:

0.0000214

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.89

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.82

MetaRNN

Benign

0.0057

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.38

PhyloP100

1.1

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

0.12

REVEL

Benign

0.038

Sift

Benign

0.62

Sift4G

Benign

0.73

Polyphen

0.0030

Vest4

0.092

MutPred

0.30

Gain of sheet (P = 0.0061)

MVP

0.41

MPC

0.23

ClinPred

0.059

GERP RS

3.4

PromoterAI

0.0012

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

gMVP

0.43

Mutation Taster

=88/12

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over